Researchers from University of Science and Technology of China have discovered Siva 1 as a novel key player in the regulation of tumor metastasis.
July 18, 2011. The renowned international multidisciplinary journal Proceedings of the National Academy of Sciences (PNAS) online published a research paper entitled “Siva1 suppresses epithelial-mesenchymal transition and metastasis of tumor cells by inhibiting stathmin and stabilizing microtubules” from Dr. Mian Wu’s Lab at University of Science and Technology of China, School of Life sciences on Tumor metastasis is depicted as a process in which cancer cells spread from a primary tumor of origin to colonize distant organs. Metastases are responsible for over 90% of deaths from cancer. Therefore, not surprisingly, it has attracted a lot of attention to the understanding of the regulation of tumor metastasis in cancer biology field. However, the detailed mechanism of tumor metastasis still remains largely unknown. The research work by Dr. Wu and his co-workers has revealed the critical role of Siva 1 in negatively regulating epithelial-mesenchymal transition (EMT) and metastasis of tumor cells. Siva 1 was found to inhibit the microtubule-destabilizing activity of Stathmin directly through binding, as well as indirectly through Ca2+/calmodulin-dependent protein kinase II-mediated phosphorylation of Stathmin at Ser 16. Via the inhibition of Stathmin, Siva 1 enhances the formation of microtubules and impedes focal adhesion assembly, cell migration, and EMT. More importantly, low levels of Siva 1 and Ser 16-phosphorylated Stathmin correlate with high metastatic states of human breast cancer cells, and knockdown of Siva 1 promotes cancer dissemination in mouse models. These results suggest that microtubule dynamics are critical for EMT. Furthermore, they reveal an important role for Siva 1 in suppressing cell migration and EMT and indicate that down-regulation of Siva 1 may contribute to tumor cell metastasis.
In the current era, anti-cancer drug discovery and development highly rely on the identification of key players in controlling tumor metastasis and understanding of their involved signaling pathways. The findings from Dr. Wu’s Lab indicate an intriguing possibility that Siva 1 may be a promissing therapeutic target for anti-metastatic therapy. In addition, levels of Siva 1 and pS16-Stathmin may be biomarkers for breast cancer.
The first author of this paper is Nan Li, a graduate student from Dr. Wu’s Lab. Part of this research work was collaborated with Dr. Xiaolu Yang from University of Pennsylvania, School of Medicine. Dr. Zhengsheng Wu from Anhui Medical University contributed to this work by providing all the clinical samples. This work was supported by the Joint Research Fund for Overseas Natural Science of China and the grants from the Chinese Academy of Sciences and the Ministry of Science and Technology.